17--nephropathy{17}.ppt

肾脏病学
nephrology-----
Glomerular Disease
Wu Hong-yan
吴红艳

Introduction of urinary system

outer layer
Glomeruli,
Proximal and distal
convoluted tubules,
Collecting ducts
inner layer
Straight portions
of the tubules,
Loops of henle,
Terminal collecting
ducts
Nephrogenesis: 2nd mo of embryonic life
Approximately 1 million nephrons /kidney
Formation of nephrons: complete before birth

Anatomic Characterizations of the urinary
system in the children
 Kidney:
lower, easy touched
 Ureter:
not straight
elastic fibers
obstruction of ureter
 Bladder:
 Urethra:
short (orifice near anus)
infection

Physiologic Characteristics of the urinary
system in the children
Kidney function of fetal:
Glomerular filtration begins around the 9th ~12thwk of fetal
life.
Renal functions: not appear, not necessary for normal
intrauterine homeostasis .
The placenta serving as the major excretory organ .
Glomerular filtration rate (GFR): the lower than in adult
Urine concentration and dilution:
Poor concentration function and nearly normal dilution
function
Renal endocrine function
renin-angiotensin, aldosterone and erythropoietin

Characteristics of the urination and urine
 Times of urination: 4-5 times/24h in the 1st wk,
20-25 times/24h 1 wk later,
6-7 times/24h in preschool or school child.
 Urine volume: normal urinary output, oliguria, anuria
Normal ~3y: 400-600ml/24h
urinary 4~7y :600-800ml/24h
volume 7~14y :800-1400ml/24h
newborn :﹤1ml/kg/h
~3y :﹤200ml/24h
oliguria 4~7y :﹤300ml/24h
7~14y :﹤400ml/24h
anuria : ﹤30~50ml/24h

 Control urination: 3 years old
Urinary quality
Colour of urine : light yellow and transparency
acidity: pH 5-7.
Protein in the urine:
negative <100mg/24h.m2; trace
+:~30mg/dl 2+: ~100mg/dl
3+:~300mg/dl 4+:~2000mg/dl

hematuria gross
microscopic
microscopic hematuria >5RBCs/HP
Cellular element and cast:
urinary sediment: RBC<3/Hp; WBC<5/Hp;
Addis count: RBC<50,000;
WBC<1000,000; cast<5000

BUN and Scr Glomerular filtration function
BUN :Newborn 1.8~6.4mmol/L，infant and children 2.5~6.4 mmol/L, adult
3.2-7.1mmol／L.
GFR＜50% , BUN↑
﹥2y, Scr =0.004×height(cm) ,GFR＜70% , Scr↑
Ccr=Ucr（μmol/L）×urinary flow（ml/min）÷Scr
（μmol/L）
Assay of β2MG in blood and urine
Blood β2MG ↑---- Glomerular filtration’s function ↓
Urine β2MG ↑ ---------renal tubule’s function ↓
Assay of enzymes in urine:
NAG ↑ -----absorption function ↓

Renal biopsy
 Purposes : to know pathological types;
to estimate prognosis;
to guide therapy
 Renal biopsy indicated for:
Persistent high-grade microscopic hematuria
Microscopic hematuria any of the following
decreased renal function;
proteinuria exceeding 100mg/24hr
hypertension
Secondary episode of gross hematuria
 contraindications:
hemorrhagic disease;
renal tumor;
acute infection of kidney and so on

Classification of glomerular diseases

Clinical classification
1. Primary glomerular diseases
1) glomerulonephritis:
acute glomerulonephritis( AGN ): APSGN
non-PSAGN
duration of disease <1yr, hematuria, proteinuria, hypertension, edema
rapidly progressive glomerulonephritis (RPGN)
disease progressing quickly, renal function is worse, bad prognosis
Persistent glomerulonephritis: the course of hematuria and or
proteinuria is>1yr and there is not renal insufficiency or hypertension.
chronic glomerulonephritis
duration of disease >1yr, renal insufficiency

2) nephrotic syndrome (NS):
clinical classification: simple type NS
nephritic type NS
corticosteroid-responsive: steroid-responsive NS
steroid-resistant NS
steroid-dependent NS
3) isolated hematuria or proteinuria
isolated hematuria: persistent and recurrent
isolated proteinuria: orthostatic and non-orthostatic

2.Secondary glomerular disesaes
1) purpura nephritis
2) lupus nephritis.
3) HBV-associated Glomerulonephritis
4) other: poison, drug, toxicosis
3. Hereditary glomerular diseases
1) congenital nephrotic syndrome
2) hereditary progressive nephritis: Alport syndrom
3) familial recurrent hematuria:

Pathological classification
1.minimal change disease(MCD)
2.focal segmental glomerulosclerosis (FSGS)
3.mesangial proliferative glomerulonephritis (MsPGN)
4.membranoprolifeative glomerulnephritis (MPGN)
5.endocapillary proliferative glomerulonephritis (ECPGN)
6. membranous glomerulonephropath (MN)
Immune classification
1.circulating immune complex nephritis
2.in situ immune complex nephritis and so on
complement has a role in capillary injury.

Acute glomerulonephritis
(AGN)

Acute glomerulonephritis
Conception
It is a common immunologic renal disease in childhood
during 5 to 14 years old. Immune reaction caused by
infections results in acute and diffuse glomeruli injury.
Acute glomerulonephritis following respiratory tract or
skin infection with hemolytic streptococci is one of the most
common forms of renal parenchymal disease in childhood.
(Acute post-streptococcal glomerulonephritis, APSGN).
The main clinical manifestations of APSGN contain the
sudden onset of gross hematuria, edema, hypertension and
renal insufficiency.

Etiology
Etiology
bacteria: “Nephritogenic” strain of group A Beta-hemolytic
streptococci represents the main causative agent in AGN.
The preceding infection can be divided into two kinds: upper
respiratory tract infection (tonsillitis, pharyngitis, sinusitis,
otitis,) and skin infection ( furuncle, pyoderma).
Viral: influenza virus, mumps virus , Coxsackie virus, ECHO
virus and EBV
Other pathogens : fungi etc.
This disease is a kind of immune-complex disease.
incidence: 10-15%

Etiology
respiratory tract infection skin infection
Latent period 1 to 2 weeks(9-11d) 3 to 4 weeks
Climate cold weather warm weather
Patient’ age early school children preschool children
Elevation of ASO usually uncommon
Serotype 12 49
anti-streptolysin O(ASO)

Circulating immunecomplexes
(CIC)
Antigens+antibodies
In situ immunecomplexes
→deposited on glomerular capillaries
→ complement system activated
→immune mediators and inflammatory
mediators↑
Pathogenesis

Normal glomerular capillary
Mesangial matrix
Mesangial cell
Endothelial cell
erythrocyte
“foot”processes
GBM
Epithelial cell

Project cytoplasmic
“Foot processes”
Endothelial cell
Glomerular basement
membrane (GBM)
Mesangial cells
Capillary cavity
Filtration barrier

Pathogenesis
edema (tonic)
group A Beta-hemolytic extracellular hypertension
Streptococcal infection fluid volume encephalopathy
circulatory congestion
antibody formation sodium,water retention
hematuria
ARF GFR GBM break proteinuria
cellular proliferation cast
Ag-Ab complex activate C3 glomerular damage
Deposition in glomerulus

Pathology
Typical pathology
diffuse, exudative and proliferative nephritis
 Chief variety
Endothelial and mesangial cells proliferation
with leukocyte infiltration;
immunofluorescence shows granular IgG & C3
deposits

光镜
On light microscopy
•glomeruli almost appear enlarged
and relatively bloodless;
•diffuse endothelial cell proliferation;
•diffuse mesangial cell proliferation
with an increase in mesangial matrix;
•Polymorphonuclear leukocytes seen

毛细血管内增生性肾小球肾炎
Endocapillary proliferative glomerulnephritis
On electron microscopy
electron-dense depositions
or “humps” on the epithelial
side of the GBM.

免疫荧光
Immunofluorescence microscopy
lumpy-bumpy deposits of
immunoglobulin and complement
on the GBM.

Clinical manifestations
 Incidence:
 a peak incidence between 6 and 7 years old;
 about 85%of cases occurring between 5 and 14 years of age
 Boys > girls = 2:1
 Preceding infection:
 90% cases suffer from preceding infection of streptococci,
such as respiratory tract infection or skin infection.
 The latent period of upper respiratory tract infection is
about 9 ~ 11 days (mean 10 days).
 The latent period of skin infection is about 14 ~28 days
(mean 20days).

 The usual clinical manifestation
(1) Abnormal urine:
 hematuria : 50~70% of cases appear gross hematuria
90% of cases appear microscopic hematuria
 proteinuria
 decrease of urine volume :
oliguria;
anuria

The usual clinical manifestation
(2) Edema:
70% of cases develop edema.
The feature of edema is non-pitting (tonic)

The usual clinical manifestation
(3) Hypertension:
30~80% of cases have hypertension.
 preschool children
Bp>120/80mmHg
 school children
Bp>130/90mmHg

 The Severe clinical manifestation
(complications)
The children with the complications are
very dangerous, the complications occur
within first 2 wk of acute nephritis.
Circulatory congestion
RR↑, HR↑, fidget , hepatomegaly, dyspnea,
jugular engorgement, pulmonary edema,
gallop rhythm and cardiac dilation

(1) Heart failure (hypervolemia, circulation volume↑):
gallop rhythm , cardiac enlargement, enlarged liver,
urinary volume decrease
Chest X-ray:
Enlarged cardiac silhouette,
lung markings coarsen
(pulmonary vascular congestion)

The Severe clinical manifestation (complications)
(2) Hypertensive encephalopathy (vasoconstriction, vasodilation)
hypertension cerebrovascular spasm hypoxia, ischemia, vascular
permeability in brain cerebral edema intracranial hypertension
persistent hypertension cerebrovascular dilation cerebral blood volume
Bp 160~200/100~140mmHg
headache, cerebral vomiting, diplopia, blindness,
convulsion, coma

The Severe clinical manifestation (complications)
(3) Acute renal failure:
oliguria ,anuria
azotemia
metabolic acidosis
hyperkalemia

Atypical findings (Atypical case)
▲Extrarenal symptomatic
nephritis
▲ Acute nephritis with nephrotic
manifestation
▲ Asymptomatic AGN

laboratory test
Blood routine test: A mild to moderate anemia,
causes: blood dilution ＆blood loss
Urine study: hematuria, proteinuria, WBC and
epithelia cells, casts (RBC ,hyaline and granular ) in
urine
cause: GBM break
Erythrocyte sedimentation rate(ESR):
cause: negative and positive charges are unbalance in
blood.
Hypocomplementemia: The serum C3 level is usually
reduced in 2 weeks and resume within 6 to 8 weeks.
cause: C3 consume

laboratory test
 Serologic evidence of preceding streptococcal infection:
positive throats exudation culture or skin pyoculture of
streptococcus;
streptozyme : anti-streptolysin O (ASO),
anti-NADase (nicotinamide adenine dinucleotidase)
anti-DPNase (diphosphopyridine nucleotidase)
anti-DNaseB (dioxyribonuclease B)
antistreptokinase
ASO titer is elevated in 10~14 days, reaches peak in
3~5wk, resumes in 3~6 mo.

laboratory test
Renal functional impairment
azotemia BUN (blood urea nitrogen)
hyperkalemia (k>5.5mmol/L)
metabolism acidosis

Diagnosis
 A history of streptococcal infection
 The manifestation of acute nephritic syndrome:
1. edema, hypertension, oliguria, hematuria,
2. proteinuria and severe complications
 Evidence of streptococcal infection:
1. elevation of ASO and streptozymes↑
 Evidence of immunolesions : complement .

Treatment
There are no specific therapy for APSGN . Heteropathy
1. Bed rest for 2 to 3 weeks
Bed rest
edema, hypertension, gross hematuria subside
allow out of bed
ESR normal
back to school
Addis count return to normal
normal activity

Treatment
2. Diet:
salt and water restriction during edema and hypertension
normal diet except during the period of edema and hypertension, and
oliguria
3. Antibiotic therapy
Penicillin or other sensitive drugs: 10 to 14 days
4. Symptomatic therapy
Diuretic: hytrochlorithiazide: 1-2mg/kg.d po
furosemide: 2-5mg/kg.d iv
Antihypertensive: nifedipine: 0.25-1mg/kg.d
captopril: 0.3-5mg/kg.d
reserpine: first dose: 0.07mg/kg(maximal dose<2mg), po or im

Treatment
5. Treatment of circulatory congestion (heart failure)
restriction of water and sodium intake
diuretic therapy (furosemide)
vasodilation (sodium nitroprusside)
dialysis
6. Treatment of hypertensive encephalopathy
sodium nitroprusside: 5-20mg+GS100ml, 1-8 μg/kg.min , iv drip
anti-convulsion: diazepam:0.3mg/kg.time(<10mg), iv
7. Treatment of acute renal failure
diuretic therapy, peritoneal dialysis or hemodialysis

Course
Course: About 2 w, The course of disease is
benign.
Routine urine test: returns to normal within
4~6w
ESR: returns to normal within 2~3 m
Addis count: 4~8 m
 Microscopic hematuria may persist for 6m~1y.

prognosis and prevention
Prognosis
Self limited disease
The long term prognosis in children is excellent, and only
2~5% cases develop chronic nephritis.
Second attacks of APSGN are rare.
 Prevention
Proper treatment of pharyngitis and skin infections;
less crowded living conditions,
It is not necessary to use long-effective penicillin.

Nephrotic syndrome (NS)
what is nephrotic syndrome?
Nephrotic syndrome is caused by increasing the
glomerular basement membrane permeability(as a
filtration barrier) to plasma proteins, which results
in a large amount of plasma protein to loss in urine.
It is characterized by massive proteinuria ,
edema, hypoproteinemia, and hyperlipidemia.

Classification
Clinical classification
Primary NS: simple type NS
nephritic type NS
Secondary NS: Collagen disease: SLE
Allergy: insect bite, snake bite.
Infection: syphilis, malaria.
Anaphylactoid purpura
Metabolic: diabetes, amyloidosis
Mechanical: renal vein thrombosis.
Congenital NS :

Classification
Classification according to curative effect of
corticosteroids (prednisone,8wks)
Steroid-responsive NS: edema extinction;
protein in the urine (—)
Steroid-resistant NS: protein in the urine
(+~++++)
Steroid-dependent NS: protein in the urine
(+)

Classification
Pathological classification
 minimal change disease（MCD，76.4%）
 focal segmental glomerulosclerosis（FSGS，6.9%）
 mesangial proliferative glomerulonephritis (MsPGN 2.3%)
 membranoproliferative glomerulonephritis（MPGN 7.5%）
 endocapillary proliferative glomerulonephritis(ECPGN
1.4%)
 membranous glomerulonephropath （ MN, 1.5%）

Normal glomerular capillary
Mesangial matrix
Mesangial cell
Endothelial cell
erythrocyte
“foot”processes
GBM
Epithelial cell
Glomerular filtration barrier with negative charges

Glomerular diseases that cause NS–--
MCD
Epidemiology:
It is most common reason of NS in
children, accounting for 80-90% of young
patients with nephrotic syndrome , while
only 20-25% in adults.
There appears to be a male
preponderance, especially in children, in
whom the male- to- female ratio is 2~3 :1

MCD
No glomerular lesions by light
microscopy
No staining with antisera specific
for immunoglobulins or
complement components.
Effacement of visceral epithelial
cell foot processes
Fusion of foot
processes

MCD
Clinical features:
The cardinal clinical feature of minimal
change glomerulopathy in children is the
relatively abrupt onset of proteinuria and
development of the NS.
Hematuria, hypertension and impaired
renal function are not common.

mesangial proliferative GN
Epidemiology:
It is a common reason of NS in our
country, accounting for 30% of primary
nephrotic syndrome, higher than those in
western.

Pathology
 Diffuse proliferation
of mesangial cells
and ECM
(extracellularmatrix)
 Positive staining with
IgA, IgG, IgM or C3 in
mesangial area
 Dense deposits in
mesangial area

Clinical features:
50% has infection before onset of renal
disease.
Non-IgAN: 50% with NS, 70% with
hematuria
IgAN:15% with NS, almost all with
hematuria

membranoproliferative glomerulonephritis, MPGN
Mesangial cells
proliferation
Thickening
GBM

membranous glomerulonephropath, MN
Fusion of
foot
processes
Thickenin
g GBM

Etiology and pathogenesis
Why does the permeability of the GBM to protein increase?
 It is unknown.
 It may be due to thymus derived (T cell) lymphocyte
function, which produces factors that increases vascular
permeability.
 It may be the abnormal Tcell function and formation of
immune complex.
electrostatic barrier damage: loss of negative charges
(selective proteinuria)
molecular barrier damage: GBM break (non- selective
proteinuria)

pathophysiology
Excessive proteinuria :
protein in urine generally exceeds 50mg/kg.d.
It is due to increased permeability of the GBM
to protein.
Hypoproteinemia is due to protein loss.
Hyperlipidemia is relatively high molecular
weight of lipoprotein . decreased level and
activity of lipases which remove lipids from
the plasma.
Edema

pathophysiology
proteinuria (basal affection)
Hypoproteinemia (key affection)
hyperlipidemia edema

Hypoproteinemia colloid osmotic pressure
transfer of fluid
blood volume
renal perfusion pressure release of antidiuretic hormone
activating
renin-angiotensin-aldosterone system
reabsorption of sodium reabsorption of water
(distal tubules) (collecting duct)
edema
colloid osmotic pressure

NS is more common in boys than girls (2.5 : 1)
occurrence of NS : more common between 2 and
6 years of age
edema: usually noticed first
A. Initial stage: mild , around the eyes
B. Active stage: generalized edema
pitting edema
ascites, hydrothorax,
hydropericardium, scrotal swelling

Complications
Infection: Causative agents: bacteria, viruses.
URI and urinary tract infection are common.
causes:
decreased immunoglobulin levels
the edema reduces the function of skin barrier
protein deficiency decreased activity of the leukocytes
immunosuppressive therapy
loss complement factors
Circulatory collapse and hypovolemia:
causes: vomiting, diarrhea, fluid shift
features: shock

Complications
Disturbance of electrolyte:
causes: restriction in diet
using diuretics
using corticosteroids
vomiting, diarrhea
features: hypokalemia
hyponatremia
hypocalcemia
hypochloremia

Complications
Tendency to arterial and venous thrombosis
causes: coagulation factors increase;
decreased level of plasma antithrombin III
increase platelet
hyperlipidemia,
features: venous thrombosis are more common than
arterial thrombosis. (kidney venous thrombosis,
pulmonary thrombosis, encephala thrombosis)

laboratory test
 Excessive proteinuria
Excretion of urine protein may be more than +++ ~ ++++ or ≥ 50mg/kg.d
bubble

laboratory test
Hypoproteinemia
The concentration of normal serum protein
rang from 60-80g/L.
albumin 35-60g/L
globulin 20-30g/L.
Hypoproteinemia: total serum protein is less
than 30-50g/L
concentration of albumin less than 25g/L.

laboratory test
 hyperlipidemia
Elevation of serum triglycerides,
phospholipids, and cholesterol.
Cholesterol level: ≥5.7mmol/L
ESR:
Other: Hematuria,
azotemia,
decreased complement C3

Diagnosis
The standards of NS diagnosis
A. Excessive proteinuria: continuance > 2 weeks
The quantity of urine protein >50mg/kg.24hr
or 3+ ~ 4+
B. Serum albumin < 25g/L
C. Plasma cholesterol > 5.7mmol/L
D. Edema
Note: A and B are necessary for diagnosis of
NS.

Diagnosis
Diagnosis of Clinical types
simple type NS
Excessive proteinuria >50mg/kg.24hr
Serum albumin < 25g/L
Plasm cholesterol > 5.7mmol/L.
Edema

Diagnosis
nephritic type NS
Besides above four features, in addition to
hematuria or hypertension or azotemia or
decreased complement C3.
RBC in the urine >5/HP
Hypertension: preschool child >120/80mmHg
school child >130/90 mmHg
Azotemia BUN
Low complement level

Differential diagnosis
Primary Secondary
children minimal change allergic purpura nephritis
Teenager mesangial proliferative FSGS
nephritis
Middle age mesengial capillary SLE LN
nephritis
old age membranous myeloma, amyloidosis
nephropathy

Treatment
General therapy
Support care
Rest
Rest in bed;
Diet
limitation of protein intake(0.8-1.0g/kg/d);
limitation of salt intake (<3g/d)
Prevention and treatment of infection

Treatment
 Diuretic:
hydrochlorithiazide: 1-2mg/kg.time po
furosemide: 1-2mg/kg.time iv or im
Proteins therapy: albumin 0.5~1.0g/kg.time
Low molecular dextran or plasma: 5-10ml/kg

Treatment
Steroid therapy
(specific therapy, the first choice of inducing NS remission)
Short term therapy: 8 weeks
The dose of prednisone : 2mg/kg.d (maximum 60mg/d),
tid for 4 weeks, following by 1.5mg/kg given as a single
morning dose on alternate days for an additional 4 weeks.
Total course : 8 weeks.
Less side-effect , but relapses are common.

Steroid therapy
Middle-term or long-term therapy:
Prednisone 1.5-2mg/kg.d (maximum 60mg/d), tid, is
given orally until the patient has protein free in urine for 2
weeks, which need 4-8 weeks, following by 2mg/kg given as a
single morning dose on alternate days for an additional 4
weeks. If the proteinuria persistent on free, and then
gradually decrease the prednisone dose.
Total course of treatment for 6 months is regarded
as middle-term therapy, for 9 months is long term
therapy.

Treatment
The side effect of
prednisolone
Cushingoid habitus,
acne
hypertension
obesity
osteoporosis
growth retardation.

Treatment
 Relapse therapy
 Prolong course of steroid therapy;
maintain small doses prednisone by 0. 25mg/kg when prednisone
decrease to 0.25mg/kg;
Total course of treatment for 1.5-2 years.
 Immunosuppressant therapy
Indications:
A. Frequent relapse:
relapses more than twice in a 6-month period.
B. Unaccepted steroid side effects
C. Steroid-resistant cases:
D. Steroid-dependent cases
 Cyclophosphamide (CTX) : 8-12mg/kg × 2d, once
per 2-4weeks, total for 9-10times.

Treatment
Immune regulator
Thymic peptide: 3-6 monthes po, im
Globulin (IgG): 400mg/kg.d for 5 days
Others
ACEI: captopril, enalapril, fosinopril
Anticoagulant:
sodium heparin, 1mg/kg.d+GS50-100ml iv drip for2-4wks
urokinase, 30,000u-60,000u/d+GS100-200ml,iv drip for 1-2 wks
dipyridamole: 5-10mg/kg.d
Traditional Chinese medicine

Treatment
The results of steroid therapy
Prednisolone 1.5-2mg/kg.d (maximum 60mg/d) tid for 8 weeks,
steroid-responsive: protein free in urine is regarded
steroid-resistant : protein + ~ ++++ in urine is regarded
steroid dependent: patient respond well to daily divided doses
of steroids but have relapse in alternate day regimen or
patient respond well to adequate steroids but have relapse in
during tapering.
frequent relapse :Initial steroid response with two or more
relapses within 6 mo
Prognosis
The prognosis for ultimate recovery is quite good.

A 8 years old boy had impetigo 4 weeks ago, He exhibit eyelid
edema 3 days ago, Amount of urine decreased and the urine is
red-coloured . He had headache , tachypnea, temporary
blindness half day ago. PE: T 36.2℃ P 160/min, R 45/min, BP
170/120mmHg, restlessness, eyelid edema and lower extremity
edema, orthopnea, Sometimes he expects forthy bloody sputum.
Fine moist rales can been heard at lower part of lungs. Heart
sound is normal without murmur. Liver is palpable 3cm below
the costal margin. Nerve system is normal. Lab tests: urine
routine : PRO ++, BLD++ . serum complement reduction.
ASO (antistreptolysin O) elevation. Questions: 1. Diagnosis 2.
Diagnostic evidence 3. Principle of treatment

17--nephropathy{17}.ppt

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